Anticholinergic compounds are well known for their property of controlling perspiration. U.S. Pat. Nos. 3,624,200 and 3,767,786 disclose and claim processes for controlling perspiration with scopolamine esters.
It is well known that anticholinergic compounds have a mydriatic effect. This mydriatic effect, though desirable in conjunction with an eye examination by an eye doctor, is an undesirable property for an antiperspirant because an accidental transfer of an anticholinergic antiperspirant to the eye can represent a significant safety problem.
As exemplified by the above-mentioned U.S. patents, the predominant anticholinergics made for antiperspirant use are scopolamine and its esters. Though the efficacy of scopolamine and its esters was demonstrated over twenty years ago, it is apparent that these compounds have not achieved widespread use as antiperspirants. This lack of use may be related to the mydriatic property referred to above, and, additionally, to the fact that ester-containing anticholinergics such as scopolamine may be cleaved by esterase activity in human perspiration, thus rendering the anticholinergic ineffective as an antiperspirant. Also, despite the fact that scopolamine is a potent anticholinergic, its antiperspirant activity is too low for commercial use.
The problems of esterase inactivation and mydriasis, discussed above, have been overcome by the use of glucuronides of anticholinergic compounds. Examples of such glucuronides are tropicamide O-.beta.-D-glucuronide and scopolamine O-.beta.-D-glucuronide, shown in Chart I. The mydriatic effect of the anticholinergics was corrected by conversion to the glucuronide. The subject invention concerns novel glucuronide compounds of anticholinergics that are effectively hydrolyzed by human sweat glucuronidase. Exemplary of these compounds are the O-.beta.-D-glucuronides of p-hydroxybenzoyl tropicamide and p-hydroxybenzoyl scopolamine. These compounds are hydrolyzed by sweat glucuronidase 20- to 80-fold more rapidly than the parent drug glucuronides. In addition, the p-hydroxybenzoyl glucuronides show no detectable mydriasis activity.